This project will clarify the differentiation, specificity and function of a population of T cells which express alphabeta antigen receptors, but lack the accessory recognition molecules CD4 and CD8. These cells are rare in normal mice and humans, but more common in autoimmune conditions. The place of these cells in differentiation will be examined by adoptive transfer of putative precursors into Thy-1 or Ly-5 congenic hosts. Their specificity and receptor repertoire will be studied by flow cytometry, to detect patterns of Vbeta use which suggest thymic selection. Cell lines and hybridomas will be developed to study the antigen specificity of the cells. Such lines will be transfected with CD4 and CD8 genes to search for occult MHC class I and II specificities. The ability of the T cell receptor to function in the absence of CD4 or CD8 will be examined by functional studies of the cells in vitro. The success of the project will shed light on the mechanism of thymic selection, and may explain the defect of self-tolerance observed in lpr/lpr mutant mice. It will also clarify the role of the accessory molecules CD4 and CD8 in T cell selection, and in peripheral T cell activation.